tbuckley/cabot-search huggingface dataset:
Higher High-Density Lipoprotein Cholesterol—Good Omen, Bad Omen, or Not an Omen at All
Authors: John Wilkins, Anand Rohatgi
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Association of Whole Blood With Survival Among Patients Presenting With Severe Hemorrhage in US and Canadian Adult Civilian Trauma Centers
Authors: Crisanto M. Torres, Alistair Kent, Dane Scantling, Bellal Joseph, Elliott R. Haut, Joseph V. Sakran
Journal: JAMA Surgery (2023)

Whole-blood (WB) resuscitation has gained renewed interest among civilian trauma centers. However, there remains insufficient evidence that WB as an adjunct to component therapy-based massive transfusion protocol (WB-MTP) is associated with a survival advantage over MTP alone in adult civilian trauma patients presenting with severe hemorrhage.
Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults
Authors: Sultana Monira Hussain, Peter R. Ebeling, Anna L. Barker, Lawrence J. Beilin, Andrew M. Tonkin, John J. McNeil
Journal: JAMA Cardiology (2023)

Increased levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing osteoblast number and function. However, the clinical significance of these findings is unclear.
Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non–Small Cell Lung Cancer
Authors: Brendan T. Heiden, Daniel B. Eaton, Su-Hsin Chang, Yan Yan, Ana A. Baumann, Martin W. Schoen, Steven Tohmasi, Nikki E. Rossetti, Mayank R. Patel, Daniel Kreisel, Ruben G. Nava, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri
Journal: JAMA Surgery (2023)

Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection.
Sleep Abnormalities in Different Clinical Stages of Psychosis
Authors: Joëlle Bagautdinova, Ahmad Mayeli, James D. Wilson, Francesco L. Donati, Rebekah M. Colacot, Nicholas Meyer, Paolo Fusar-Poli, Fabio Ferrarelli
Journal: JAMA Psychiatry (2023)

Abnormal sleep is frequent in psychosis; however, sleep abnormalities in different stages (ie, clinical high risk for psychosis [CHR-P], early psychosis [EP], and chronic psychosis [CP]) have not been characterized.
Differences in Insurance Coverage for Individuals With Schizophrenia After Implementation of the Patient Protection and Affordable Care Act
Authors: Kimberley H. Geissler, Keith M. Ericson, Gregory E. Simon, Jing Qian, John E. Zeber
Journal: JAMA Psychiatry (2023)

This cross-sectional study uses Medical Expenditure Panel Survey data to assess differences in insurance coverage for individuals with schizophrenia before vs after implementation of the Patient Protection and Affordable Care Act (ACA).
Etomidate vs Propofol in Older Surgical Patients
Authors: Na Jing, Ayong Tian
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe
Authors: Margo J. Reeder, Erin Warshaw, Srikanth Aravamuthan, Donald V. Belsito, Johannes Geier, Mark Wilkinson, Amber Reck Atwater, Ian R. White, Jonathan I. Silverberg, James S. Taylor, Joseph F. Fowler, Howard I. Maibach, Joel G. DeKoven, Timo Buhl, Nina Botto, Ana Maria Giménez-Arnau, Rosella Gallo, Christen Mowad, Claudia C. V. Lang, Vincent A. DeLeo, Graham Johnston, Melanie D. Pratt, Knut Brockow, Brandon L. Adler, Marie-Claude Houle, Heinrich Dickel, Marie Louise A. Schuttelaar, JiaDe Yu, Radoslaw Spiewak, Cory Dunnick, Francesca Larese Filon, Skaidra Valiukevičienė, Wolfgang Uter
Journal: JAMA Dermatology (2023)

The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US.
Whole-Blood Resuscitation Following Traumatic Injury and Hemorrhagic Shock—Should It Be Standard Care?
Authors: Jason L. Sperry, Joshua B. Brown
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study
Authors: Han-Min Wang, Chan-Yuan Zhang, Kai-Cheng Peng, Ze-Xin Chen, Jun-Wei Su, Yu-Fa Li, Wen-Feng Li, Qing-Yun Gao, Shi-Ling Zhang, Yu-Qing Chen, Qing Zhou, Cong Xu, Chong-Rui Xu, Zhen Wang, Jian Su, Hong-Hong Yan, Xu-Chao Zhang, Hua-Jun Chen, Yi-Long Wu, Jin-Ji Yang
Journal: Cell Reports Medicine (2023)

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.
Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases
Authors: Tuomo Kiiskinen, Pyry Helkkula, Kristi Krebs, Juha Karjalainen, Elmo Saarentaus, Nina Mars, Arto Lehisto, Wei Zhou, Mattia Cordioli, Sakari Jukarainen, Joel T. Rämö, Juha Mehtonen, Kumar Veerapen, Markus Räsänen, Sanni Ruotsalainen, Mutaamba Maasha, Teemu Niiranen, Tiinamaija Tuomi, Veikko Salomaa, Mitja Kurki, Matti Pirinen, Aarno Palotie, Mark Daly, Andrea Ganna, Aki S. Havulinna, Lili Milani, Samuli Ripatti
Journal: Nature Medicine (2023)

Abstract Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci ( P &lt; 5 × 10 –9 ) associated with medication use. Fine-mapping revealed 494 95% credible sets associated with the total number of medication purchases, changes in medication combinations or treatment discontinuation, including 46 credible sets in 40 loci not associated with the underlying treatment targets. The polygenic risk scores (PRS) for cardiometabolic risk factors were strongly associated with the medication-use behavior. A medication-use enhanced multitrait PRS for coronary artery disease matched the performance of a risk factor-based multitrait coronary artery disease PRS in an independent sample (UK Biobank, n = 343,676). In summary, we demonstrate medication-based strategies for identifying cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases.
Cardiac splicing as a diagnostic and therapeutic target
Authors: Michael Gotthardt, Victor Badillo-Lisakowski, Victoria Nicole Parikh, Euan Ashley, Marta Furtado, Maria Carmo-Fonseca, Sarah Schudy, Benjamin Meder, Markus Grosch, Lars Steinmetz, Claudia Crocini, Leslie Leinwand
Journal: Nature Reviews Cardiology (2023)
<i>NFE2L2</i>Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells
Authors: Li Guan, Dhanya K. Nambiar, Hongbin Cao, Vignesh Viswanathan, Shirley Kwok, Angela B. Hui, Yuan Hou, Rachel Hildebrand, Rie von Eyben, Brittany J. Holmes, Junfei Zhao, Christina S. Kong, Nathan Wamsley, Weiruo Zhang, Michael B. Major, Seung W. Seol, John B. Sunwoo, D. Neil Hayes, Maximilian Diehn, Quynh-Thu Le
Journal: Cancer Research (2023)

Abstract Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found that mutations in NFE2L2, which encodes Nrf2, are associated with a significantly higher rate of LRF in patients with oral cavity cancer treated with surgery and adjuvant (chemo)radiotherapy but not in those treated with surgery alone. Somatic mutation of NFE2L2 led to Nrf2 activation and radioresistance in HNSCC cells. Tumors harboring mutant Nrf2E79Q were substantially more radioresistant than tumors with wild-type Nrf2 in immunocompetent mice, whereas the difference was diminished in immunocompromised mice. Nrf2E79Q enhanced radioresistance through increased recruitment of intratumoral polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and reduction of M1-polarized macrophages. Treatment with the glutaminase inhibitor CB-839 overcame the radioresistance induced by Nrf2E79Q or Nrf2E79K. RT increased expression of PMN-MDSC–attracting chemokines, including CXCL1, CXLC3, and CSF3, in Nrf2E79Q-expressing tumors via the TLR4, which could be reversed by CB-839. This study provides insights into the impact of NFE2L2 mutations on radioresistance and suggests that CB-839 can increase radiosensitivity by switching intratumoral myeloid cells to an antitumor phenotype, supporting clinical testing of CB-839 with RT in HNSCC with NFE2L2 mutations. Significance: NFE2L2 mutations are predictive biomarkers of radioresistance in head and neck cancer and confer sensitivity to glutaminase inhibitors to overcome radioresistance.
Melatonin‐Primed Mesenchymal Stem Cells‐Derived Small Extracellular Vesicles Alleviated Neurogenic Erectile Dysfunction by Reversing Phenotypic Modulation
Authors: Zehong Chen, Jiancheng Zhai, Jiahui Ma, Peng Chen, Weishun Lin, Weipeng Zhang, Jiaming Xiong, Chaowei Zhang, Hongbo Wei
Journal: Advanced Healthcare Materials (2023)

Erectile dysfunction (ED) is an adverse side effect of pelvic surgery with no effective treatment. In this study, it is explored whether melatonin could improve the therapeutic effects of small extracellular vesicles (sEVs), derived from mesenchymal stem cells (MSCs), on cavernous nerve injury (CNI) ED, and the underlying mechanisms are investigated. The sEVs from melatonin-pretreated MSCs (MT-EVs) and MSCs (NC-EVs) are isolated and applied to CNI ED. Transplantation of MT-EVs remarkably increases erectile function and reduces phenotypic modulation in CNI ED rats. The therapeutic effects of MT-EVs are superior to those of NC-EVs. Sequencing implies that miR-10a-3p is enriched in MT-EVs, and directly targets the protein kinase inhibitor α (PKIA). After the suppression of miR-10a-3p, the therapeutic actions of MT-EVs are abolished, but are rescued by PKIA. Similarly, RhoA/ROCK is inhibited by MT-EVs, but this action is reversed by suppressing miR-10a-3p, accompanied by corresponding changes in PKIA. In conclusion, transplantation of MT-EVs could significantly alleviate CNI ED. MT-EVs may relieve the phenotypic modulation of the corpora cavernosum smooth muscle cells via the miR-10a-3p/PKIA/RhoA/ROCK signaling axis. These nanovesicles should be potential therapeutic vectors or bioactive materials for CNI ED.
Architecture‐Engineered Electrospinning Cascade Regulates Spinal Microenvironment to Promote Nerve Regeneration
Authors: Yu Tang, Zonghan Xu, Jincheng Tang, Yichang Xu, Ziang Li, Wenbo Wang, Liang Wu, Kun Xi, Yong Gu, Liang Chen
Journal: Advanced Healthcare Materials (2023)

The inflammatory cascade after spinal cord injury (SCI) causes necrotizing apoptosis of local stem cells, which limits nerve regeneration. Therefore, coordinating the inflammatory immune response and neural stem cell (NSC) functions is key to promoting the recovery of central nervous system function. In this study, a hydrogel "perfusion" system and electrospinning technology are integrated, and a "concrete" composite support for the repair of nerve injuries is built. The hydrogel's hydrophilic properties activate macrophage integrin receptors to mediate polarization into anti-inflammatory subtypes and cause a 10% increase in polarized M2 macrophages, thus reprogramming the SCI immune microenvironment. Programmed stromal cell-derived factor-1α and brain-derived neurotrophic factor released from the composite increase recruitment and neuronal differentiation of NSCs by approximately four- and twofold, respectively. The fiber system regulates the SCI immune inflammatory microenvironment, recruits endogenous NSCs, promotes local blood vessel germination and maturation, and improves nerve function recovery in a rat SCI model. In conclusion, the engineering fiber composite improves the local inflammatory response. It promotes nerve regeneration through a hydrophilic programmed cytokine-delivery system, which further improves and supplements the immune response mechanism regulated by the inherent properties of the biomaterial. The new fiber composite may serve as a new treatment approach for SCI.
A Phase I Dose-escalation Study of AZD3965, an Oral Monocarboxylate Transporter 1 Inhibitor, in Patients with Advanced Cancer
Authors: Sarah Halford, Gareth J. Veal, Stephen R. Wedge, Geoffrey S. Payne, Chris M. Bacon, Philip Sloan, Ilaria Dragoni, Kathrin Heinzmann, Sarah Potter, Becky M. Salisbury, Maxime Chénard-Poirier, Alastair Greystoke, Elizabeth C. Howell, William A. Innes, Karen Morris, Chris Plummer, Mihaela Rata, George Petrides, Hector C. Keun, Udai Banerji, Ruth Plummer
Journal: Clinical Cancer Research (2023)

Inhibition of monocarboxylate transporter (MCT) 1-mediated lactate transport may have cytostatic and/or cytotoxic effects on tumor cells. We report results from the dose-escalation part of a first-in-human trial of AZD3965, a first-in-class MCT1 inhibitor, in advanced cancer.
Event-Free Survival as a Surrogate for Overall Survival in Gastric and Gastroesophageal Junction Adenocarcinoma: A Meta-analysis in the Neoadjuvant ± Adjuvant Setting
Authors: Zev A. Wainberg, Jipan Xie, Adriana Valderrama, Lei Yin, Shujing Zhang, Chie-Schin Shih, Pooja Bhagia, Qianqian Gu, Kohei Shitara, Yelena Y. Janjigian, Josep Tabernero
Journal: Clinical Cancer Research (2023)

Abstract Purpose: This study assessed the trial-level association between event-free survival (EFS) and overall survival (OS) in gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant ± adjuvant settings. Experimental Design: A systematic literature review was conducted to identify randomized controlled trials (RCT) that evaluated neoadjuvant therapies with or without adjuvant therapies for gastric or GEJ adenocarcinoma. A meta-analysis was performed using weighted linear regressions of the treatment effect of OS on the treatment effect of EFS. The coefficient of determination (R²) and associated 95% confidence interval (CI) were used to evaluate the association between treatment effects of EFS and OS. The threshold used for defining good trial-level surrogacy was a correlation coefficient (R) of 0.8 or R² of 0.65, based on prior literature. Sensitivity analyses were performed to assess the robustness of the association with divergent study designs, including study population, inclusion of adjuvant therapy, and definitions of EFS and OS. Results: The main analysis included 16 comparisons from 15 RCTs. The log(HR) of EFS was a significant predictor of log(HR) of OS, with an estimated coefficient of 0.72 (P &amp;lt; 0.001) and R² = 0.75 (95% CI, 0.49–0.95), indicating that EFS was a good surrogate outcome for OS. The results of the sensitivity analyses were consistent with the primary results, with R² ranging from 0.76 to 0.89. Conclusions: This study suggests that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in the neoadjuvant ± adjuvant setting.
Dual mTORC1/2 Inhibition Synergistically Enhances AML Cell Death in Combination with the BCL2 Antagonist Venetoclax
Authors: Toshihisa Satta, Lin Li, Sri Lakshmi Chalasani, Xiaoyan Hu, Jewel Nkwocha, Kanika Sharma, Maciej Kmieciak, Mohamed Rahmani, Liang Zhou, Steven Grant
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Acute myelogenous leukemia (AML) is an aggressive disease with a poor outcome. We investigated mechanisms by which the anti-AML activity of ABT-199 (venetoclax) could be potentiated by dual mTORC1/TORC2 inhibition. Experimental Design: Venetoclax/INK128 synergism was assessed in various AML cell lines and primary patient AML samples in vitro. AML cells overexpressing MCL-1, constitutively active AKT, BAK, and/or BAX knockout, and acquired venetoclax resistance were investigated to define mechanisms underlying interactions. The antileukemic efficacy of this regimen was also examined in xenograft and patient-derived xenograft (PDX) models. Results: Combination treatment with venetoclax and INK128 (but not the mTORC1 inhibitor rapamycin) dramatically enhanced cell death in AML cell lines. Synergism was associated with p-AKT and p-4EBP1 downregulation and dependent upon MCL-1 downregulation and BAK/BAX upregulation as MCL-1 overexpression and BAX/BAK knockout abrogated cell death. Constitutive AKT activation opposed synergism between venetoclax and PI3K or AKT inhibitors, but not INK128. Combination treatment also synergistically induced cell death in venetoclax-resistant AML cells. Similar events occurred in primary patient-derived leukemia samples but not normal CD34+ cells. Finally, venetoclax and INK128 co-treatment displayed increased antileukemia effects in in vivo xenograft and PDX models. Conclusions: The venetoclax/INK128 regimen exerts significant antileukemic activity in various preclinical models through mechanisms involving MCL-1 downregulation and BAK/BAX activation, and offers potential advantages over PI3K or AKT inhibitors in cells with constitutive AKT activation. This regimen is active against primary and venetoclax-resistant AML cells, and in in vivo AML models. Further investigation of this strategy appears warranted.
Allergy: Mechanistic insights into new methods of prevention and therapy
Authors: Cezmi A. Akdis, Mübeccel Akdis, Scott D. Boyd, Vanitha Sampath, Stephen J. Galli, Kari C. Nadeau
Journal: Science Translational Medicine (2023)

In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.